VITAMIN D3 AND ANALOGS THEREOF FOR ALLEVIATING SIDE EFFECTS ASSOCIATED WITH CHEMOTHERAPY

• US 20100196308A1
• Filed: 01/27/2010
• Published: 08/05/2010
• Est. Priority Date: 01/27/2009
• Status: Abandoned Application

• Current Assignee: Berg LLC (BPGbio Inc)
• Original Assignee: Berg LLC (BPGbio Inc)
• Inventors: Jimenez, Joaquin J., McCook, John Patrick, Narain, Niven Rajin
• Application Number:
  US12/695,113
• Publication Number:
  US 20100196308A1
• Time in Patent Office: Days
• US Class Current: 424/85.1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/593 9,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3
• CPC Class Codes: A61K 38/1816 Erythropoietin [EPO]
• CPC Class Codes: A61K 38/193 Colony stimulating factors [CSF]
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/04 Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 7/06 Antianaemics

Abstract

The present disclosure relates to the use of vitamin D compounds, such as vitamin D3, or analogs and/or metabolites thereof, to modulate bone marrow progenitors and stromal cells prior to the administration of antineoplastic agents. The methods of the present disclosure may ameliorate myelosuppression by increasing the availability of pluripotent stem cell progenitors, and can be used in combination with standard therapy (e.g. granulocyte stimulating factor) to increase proliferation of myeloid cells and/or improve their mobilization from the bone marrow, thereby diminishing the dose and administration of colony-stimulating factors (CSFs) as well as the recuperation time following chemotherapy.

Claims

1. A method of preventing or reducing chemotherapy-induced myelosuppression in a subject being treated with a chemotherapeutic agent which induces myelosuppression, comprising administering to the subject an effective amount of a vitamin D compound or a pharmaceutically acceptable salt, prodrug or solvate thereof.

2. The method of claim 1, wherein the vitamin D compound is of Formula (I):

3. The method of claim 1, wherein the vitamin D compound is represented by Formula (II):

4. The method of claim 1, wherein said vitamin D compound comprises 1,25-dihydroxyvitamin D3;

1,25-dihydroxy-16-ene-23-yne-cholecalciferol;

1,25-dihydroxy-16-ene-yne-cholecalciferol;

1α

-hydroxyvitamin D3;

1α

,24-dihydroxyvitamin D3, MC 903, or combinations thereof.

5. The method of claim 1, wherein said vitamin D compound is administered topically or systemically.

6. The method of claim 1, wherein the chemotherapy involves the use of a cell cycle-specific chemotherapeutic agent.

7. The method of claim 1, wherein the chemotherapy involves the use of a nonspecific cell cycle chemotherapeutic agent.

8. The method of claim 1, wherein the chemotherapeutic agent is a cell cycle-specific agent in combination with a nonspecific cell cycle agent.

9. The method of claim 1, wherein said vitamin D compound is administered prior to the administration of said chemotherapeutic agent.

10. The method of claim 1, wherein said vitamin D compound is co-administered with said chemotherapeutic agent.

11. The method of claim 1, wherein the subject is a mammal.

12. The method of claim 1, wherein the vitamin D compound is co-administered with an additional agent that counteracts chemotherapy-induced anemia.

13. The method of claim 12, wherein the agent is a growth factor.

14. The method of claim 13, wherein said growth factor is G-CSF or EPO.

15. The method of claim 1, wherein the vitamin D compound is formulated as a sterile solution comprising between about 50 μ

g/mL and about 400 μ

g/mL of the vitamin D compound.

16. The method of claim 15, wherein the formulation further comprises anhydrous undenatured ethanol and polysorbate 20.

17. The method of claim 15, wherein the formulation is diluted 1:

10 in 0.9% sodium chloride solution prior to administration to the subject.

18. The method of claim 15, wherein the formulation comprises about 75 μ

g/mL vitamin D compound.

19. The method of claim 15, wherein the formulation comprises about 345 μ

g/mL vitamin D compound.

20. The method of claim 15, wherein the vitamin D compound is calcitriol.

21. A method to determine an optimal therapeutic dose of a vitamin D compound, comprising

administering to a subject a series of test amounts of the vitamin D compound or a pharmaceutically acceptable salt thereof, and

determining the minimal dose required to protect the myeloid cells of the subject from chemotherapy-induced myelosuppression without eliciting a hypercalcemic effect, wherein the vitamin D compound is represented by Formula (I):

22. A method of reducing the risk of or preventing a myelosuppression-induced disorder in a subject being treated with a chemotherapeutic agent that induces myelosuppression, comprising administering to the subject an effective amount of a vitamin D compound or a pharmaceutically acceptable salt, prodrug or solvate thereof such that said myelosuppression-induced disorder is prevented of the risk of myelosuppression-induced disorder is reduced.

23. The method of claim 22, wherein said myelosuppression-induced disorder is myelosuppression-induced infection.

24. A methods of preventing depletion of neutrophils in a subject being treated with a chemotherapeutic agent comprising, administering to the subject an effective amount of a vitamin D compound or a pharmaceutically acceptable salt, prodrug or solvate thereof, such that the depletion of neutrophils in said subject is prevented.